The ability of cells to form cell contacts, adhere to the extracellular matrix, change morphology, and migrate is essential for development, wound healing, metastasis, cell survival and the immune response. These events depend on the binding of integrin to the extracellular matrix, and assembly of focal adhesions, which are complexes of scaffolding and signaling proteins organized by adhesion to the extracellular matrix (Critchley (2000) Curr. Opin. Cell Biol. 12:133–139; Burridge and Chrzanowska-Wodnicka (1996) Annu. Rev. Cell Dev. Biol. 12:463–518; Schwartz and Ginsberg (2002) Nature Cell Biol. 4:E65–E68). Phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P2) regulates interactions between these proteins, including the interaction of vinculin with actin and talin (McNamee, et al. (1993) J. Cell Biol. 121:673–678; Berditchevski, et al. (1997) J. Biol. Chem. 272:2595–2598; Chong, et al. (1994) Cell 79:507–513; Gilmore and Burridge (1996) Nature 381:531–535; Steimle, et al. (1999) J. Biol. Chem. 274:18414–18420; Martel, et al. (2001) J. Biol. Chem. 276:21217–21227). The binding of talin to β-integrin is strengthened by PtdIns(4,5)P2, suggesting that the basis of focal adhesion assembly is regulated by this lipid mediator (Martel, et al. (2001) supra; Janmey (1994) Annu. Rev. Physiol. 56:169–191). Further, it has been suggested that PIPKIγ661/talin association is important for targeting PIPKIγ661 to focal adhesions (Di Paolo, et al. (2002) Nature 420:85–89; Ling, et al. (2002) Nature 420:89–93).